Table 2 MSC-based protocols to generate beta cell-like cells
Source/type of MSC | Method | Endodermal differentiation | Pancreatic or endocrine differentiation | Maturation | Genes analyzed | Efficiency | In vivo testing reported | Functional analysis | Protocol duration in days | Reference |
|---|---|---|---|---|---|---|---|---|---|---|
Umbilical cord | Extracellular matrix | – | – | – | NA | 25.2 | No | – | 9 | [64] |
Umbilical cord | Small molecule | – | Nicotinamide in high glucose | C-peptide | – | No | – | 7 | [65] | |
Umbilical cord | ECM + small molecule + GF | – | High-glucose, retinoic acid, nicotinamide, EGF | FBS and exendin-4 | Insulin, glucagon, Glut-2, PDX1, PAX4, NGN3 | 25 | No | EM | 15 | [66] |
Umbilical cord | Small molecule + peptide | – | High glucose, nicotinamide, exendin-4, 2-mercaptoethanol | Insulin,PDX1, glucagon | – | No | Nil | 7 | [67] | |
Umbilical cord blood | Plasmid electro transfer | – | PDX1 plasmid electro transfer | PDX1, Ngn3, NKX6.1 | 82.94 (PDX1 +ve cells) | No | Nil | 10 | [68] | |
Wharton jelly | Small molecule + GF | – | High glucose and RA, L-nicotinic acid and EGF | FBS and exendin-4 | PDX1, NGN3, Glut2, and insulin | – | No | Dithizone staining, c-pep quantification | 14 | [69] |
Placenta | Small molecule + peptide | – | l-Taurine and BSA | l-Taurine, nicotinamide, GLP-1, BSA | Insulin, glucagon, somatostatin | 65 | Yes | c-pep/insulin quantification, dithizone staining | 20 | [61] |
Bone marrow | Small molecule + peptide | – | High glucose and nicotinamide | Exendin-4 | PDX1, NGN3, NKX6.1, PAX4, Glut 2, glucagon, insulin | 43 | Yes | Dithizone staining, EM, c-pep quantification, calcium imaging | 29 | [70] |
Bone marrow | Small molecule + GF | – | bFGF, high glucose, and nicotinamide | Nicotinamide, Activin A, and exendin 4 | NKX6.1, ISL-1, NEUROD 1, Glut2, Pax6, PDX1, NGN3, insulin and glucagon | 38.9 | Yes | Dithizone staining, EM, c-pep quantification | 15 | [71] |
Bone marrow | Adenoviral transfection | Transfection using PDX1 or VEGF | Insulin | 50 | Yes | – | 2 | [72] | ||
Bone marrow | Small molecule + peptide | – | Nicotinamide and exendin-4 | PDX1, NGN3, PAX4, IAPP, and insulin | 20 | Yes | – | 5 | [73] | |
Bone marrow | Small molecule + GF | – | BFGF, EGF | Nicotinamide, Activin, Betacellulin | PDX1, MAF-A,B, NGN3, PAX4, insulin, c-peptide | 5 | Yes | EM | 18 | [74] |
Bone marrow | Viral transfection | – | Lentiviral transfection of miR-375 and anti-miR-9. | PDX1, NKX6., FoxA2, GCG, insulin, NGN3 | 85 | No | Dithizone staining, c-pep quantification | 21 | [75] | |
Urine | Small molecules | IDE1, vitamin C | Indolactam V, retinoic acid | Nicotinamide, DAPT, SB203580 | Sox-17, FoxA2, PDX1, NKX6.1, insulin, c-peptide | 80 | No | c-pep quantification | 30 | [76] |
Dental | Small molecules + peptide | – | High glucose and retinoic acid | Low glucose, nicotinamide, EGF, Exendin A, Activin A, indolactam V | PDX1, NKx6.1, NGN3, Glut2, MAfA | – | No | c-pep quantification, dithizone staining | 21 | [77] |
Adipose | Small molecule + peptide | Sodium butyrate and high glucose | l-Taurin | Nicotinamide and GLP-1 | Hnf3β, TCF2, Sox17, PDX1, Ngn3, NeuroD, PAX4 | – | No | – | 16–18 | [78] |
Bone marrow | Retroviral infection | – | PDX1 infection and culturing in bFGF | PDX1, NeuroD1, NGN3, NKX6.1, ISl1 | 40–70 | Yes | c-pep/insulin quantification | 21 | [72] | |
Bone marrow | Adenoviral transfection | – | PDX1 infection and culturing in GLP 1 | NGN3, insulin, GK, Glut2, and glucagon | – | Yes | c-pep/insulin quantification, calcium imaging | 14 | [79] | |
Bone marrow | Serum-free culture | – | Serum-free media culture | NGN3, Brn4, NKX6.1, PAX6, and Isl1 | 33 | Yes | c-pep quantification | 6–7 | [80] | |
Serum free + small molecules + GF | – | 1. High glucose and conophylline | PDX1, insulin, glucagon | ~ 2.5 for all protocols | No | Dithizone staining, c-peptide quantification | 15 | [81] | ||
– | 2. High glucose, trichostatin and GLP-1 | 10 | ||||||||
– | 3. High glucose and 2-ME, bFGF and EGF, betacellulin, nicotinamide, and activin | 18 | ||||||||
Bone marrow | Adenoviral transfection | – | Infection of IPF1, HLXB9, and FOXA2 | PDX1, NEUROD1, NKX6.2, Pax 6 | 50 | No | – | 14 | [82] | |
Adipose | Small molecules + GF | – | High glucose, nicotinamide, Exendin, HGF, pentagastrin, activin A | Isl-1, Ipf-1, NGN, insulin, glucagon | 10 | Yes | – | 3 | [83] | |